title: Enhanced fear expression in a psychopathological mouse model of trait anxiety: pharmacological interventions.
abstract: The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors. Here we investigated the relationship between a genetic predisposition to trait anxiety and experience-based learned fear in a psychopathological mouse model. Male CD-1 mice selectively bred for either high (HAB), or normal (NAB) anxiety-related behaviour on the elevated plus maze were subjected to classical fear conditioning. During conditioning both mouse lines showed increased fear responses as assessed by freezing behaviour. However, 24 h later, HAB mice displayed more pronounced conditioned responses to both a contextual or cued stimulus when compared with NAB mice. Interestingly, 6 h and already 1 h after fear conditioning, freezing levels were high in HAB mice but not in NAB mice. These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line. The enhanced fear response of HAB mice was attenuated by treatment with either the α(2,3,5)-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429. Overall, the HAB mouse line may represent an interesting model (i) for identifying biological factors underlying misguided conditioned fear responses and (ii) for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias.
authors.affiliation: Department of Pharmacology and Toxicology, Center for Molecular Biosciences Innsbruck and Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria. simone.sartori@uibk.ac.at
authors.forename: Simone B
authors.initials: SB
authors.lastname: Sartori
authors.forename: Markus
authors.initials: M
authors.lastname: Hauschild
authors.forename: Mirjam
authors.initials: M
authors.lastname: Bunck
authors.forename: Stefano
authors.initials: S
authors.lastname: Gaburro
authors.forename: Rainer
authors.initials: R
authors.lastname: Landgraf
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000150:complications / Q000188:drug therapy* / Q000473:pathology* / Q000523:psychology; D001522:Behavior, Animal; D003345:Corticosterone / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D019260:Expressed Emotion / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005464:Fluorobenzenes / Q000627:therapeutic use; D008297:Male; D051379:Mice; D064729:Neurokinin-1 Receptor Antagonists; D010698:Phobic Disorders / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D010805:Physical Conditioning, Animal / Q000502:physiology / Q000523:psychology; D010880:Piperidines / Q000627:therapeutic use; D011599:Psychopathology; D014230:Triazoles / Q000627:therapeutic use; D015854:Up-Regulation
chemical_list: D014151:Anti-Anxiety Agents; D005464:Fluorobenzenes; C532739:N-((2-cyclopropoxy-5-(5-trifluomethyl)tetrazol-1-yl)benzyl)-2-phenylpiperidin-3-amine; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D014230:Triazoles; C409903:L 838,417; D003345:Corticosterone